Lipid Management in Renal Transplant Recipients Using Evolocumab.

NCT ID: NCT04608474

Last Updated: 2023-07-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-17
• Study Completion Date: 2024-12-31

Brief Summary

Cardiovascular disease is the leading cause of mortality after renal transplantation, accounting for more than 30% of deaths. Elevated lipid levels (hyperlipidemia) are a frequent finding following transplantation and the immunosuppressive medications play a central role in the development or worsening of hyperlipidemia. In the general population, the correlation between elevated serum cholesterol and increased risk of cardiovascular disease is well established and the reduction in serum LDL cholesterol has proved to significantly reduce both morbidity and mortality.

Statin based drugs are the standard of care in the management of hyperlipidemia. Commonly used statin-based drugs include atorvastatin (Lipitor), fluvastatin (Lescol, Lescol XL), lovastatin (Mevacor, Altoprev), pravastatin (Pravachol), rosuvastatin (Crestor), simvastatin (Zocor), and pitavastatin (Livalo). These drugs have been proven to lower lipid levels as well as cardiovascular risk. However, statin-based drugs also cause a variety of side effects. While the most commonly encountered side effects are toxicity to the liver and muscles, a few others have also been known to cause increased excretion of protein in the urine and kidney failure. These side effects are also more common in a renal transplant recipient due to the simultaneous administration of drugs that prevent rejection. Therefore, there is an emergent need for newer drugs which are both efficient and safe especially in this population PCSK-9 inhibitors (Proprotein Convertase Subtilisin Kinase-9 inhibitors) are a new class of drugs that are highly efficient in lowering lipid levels in the general population. However, an exclusive trial involving kidney transplant recipients is yet to be done. Through this study, we would like to evaluate the safety and tolerability of Evolocumab (trade name: Repatha) which is a PCSK-9 inhibitor developed by Amgen, Inc in renal transplant recipients. The study would involve a total of 120 patients across 3 different hospitals in Boston, Massachusetts.

Detailed Description

Cardiovascular disease is the leading cause of death in renal transplant recipients (RTR). 44% of RTR have LDL-C greater than 100mg/dL, six months after transplant. The correlation between the increase in serum LDL level and the increased risk of atherosclerotic cardiovascular disease (ASCVD) is well established. A reduction in LDL level is associated with a decreased risk of mortality and morbidity in patients with ASCVD. Statins have been the long-standing drug of choice in treating dyslipidemia. A single prospective randomized trial known as the ALERT trial compared the benefits of statins to placebo in transplant recipients. The original study consisted of 2000 RTR and an extension of this study evaluated 1652 patients and demonstrated a 21% reduction in major cardiac events (p=0.036) and a 29% reduction in cardiac death or definite non-fatal myocardial infarction (p=0.014). Even though statins decrease the probability of cardiovascular events there was no difference in graft survival or mortality benefit in RTR. Another concerning factor for the use of statins is the tolerability of these drugs. Statins have been associated with hepatotoxicity and myotoxicity, the incidence of which is higher in RTR. This effect is dose-related and may be precipitated by the administration of agents that inhibit cytochrome p450 isoenzymes such as Tacrolimus and Cyclosporine which are the most commonly used immunosuppressants. Another statin based drug (Fluvastatin) has been associated with proteinuria and renal failure. Hence there is a need to explore novel treatment options in the management of dyslipidemia, particularly in RTR. PCSK-9 inhibitors (Proprotein Convertase Subtilisin Kinase-9 inhibitors) have shown to decrease LDL levels by 60% in patients on statin therapy. However, these drugs have been studied sparingly in patients with Chronic Kidney Disease (CKD) and have not yet been analyzed in RTR.

The study will involve 120 patients across 3 different hospitals. Two different but equivalent drug dosing strategies are available. A 420mg monthly subcutaneous injection using an on-body infusor (Repatha Pushtronex system) or a 140mg subcutaneous injection once every two weeks using a prefilled auto-injector (Repatha SureClick). The choice of dosing strategy will be based on patient preference. This study will be conducted over one year.

Conditions

Hyperlipidemias

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Evolocumab only

This arm includes subjects who are treated using Evolocumab.

Group Type: EXPERIMENTAL

Evolocumab

Intervention Type: DRUG

Two different but equivalent drug dosing strategies are available. A 420mg monthly subcutaneous injection using an on-body infuser (Repatha Pushtronex system) or a 140mg subcutaneous injection once every two weeks using a prefilled auto-injector (Repatha SureClick). The choice of dosing strategy will be based on patient preference.

Evolocumab plus statin

This arm includes subjects who are treated using a combination of Evolocumab and a statin-based drug.

Group Type: EXPERIMENTAL

Evolocumab

Intervention Type: DRUG

Two different but equivalent drug dosing strategies are available. A 420mg monthly subcutaneous injection using an on-body infuser (Repatha Pushtronex system) or a 140mg subcutaneous injection once every two weeks using a prefilled auto-injector (Repatha SureClick). The choice of dosing strategy will be based on patient preference.

Statins (Cardiovascular Agents)

Intervention Type: DRUG

Previously prescribed statin therapy.

Interventions

Evolocumab

Two different but equivalent drug dosing strategies are available. A 420mg monthly subcutaneous injection using an on-body infuser (Repatha Pushtronex system) or a 140mg subcutaneous injection once every two weeks using a prefilled auto-injector (Repatha SureClick). The choice of dosing strategy will be based on patient preference.

Intervention Type: DRUG

Statins (Cardiovascular Agents)

Previously prescribed statin therapy.

Intervention Type: DRUG

Other Intervention Names

Rapatha; HMG CoA reductase inhibitors

Eligibility Criteria

Inclusion Criteria

• Adult renal transplant recipients greater than 1-year post-transplantation, men and women between 18 and 85 years of age, inclusive.
• Any patient with documented ASCVD or diabetes and 1 or more risk factors for ASCVD, including, but not limited to obesity, inactive lifestyle, hypertension, smoking, and family history. and an LDL >70 mg/dl (Highest-Risk Patients)
• Any patient not classified as one of our highest-risk patients, that has an LDL >100 mg/dl

Exclusion Criteria

• Patients currently enrolled in another interventional clinical trial.
• Patients being actively treated for cellular or antibody-mediated rejection.
• Serious hypersensitivity to Evolocumab or any component of the formulation.
• Patients who are pregnant or planning a pregnancy in the next one year.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Anil K. Chandraker, MD

Medical Director, Kidney and Pancreas Transplantation

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anil K Chandraker, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Anil K Chandraker, MD

Role: CONTACT

achandraker@bwh.harvard.edu

617-732-7412

Facility Contacts

Rohan Saranu

Role: primary

rsaranu@bwh.harvard.edu

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Other Identifiers

2020P000437

Identifier Type: -

Identifier Source: org_study_id